Browsing by Author "Parmar, A"
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- ItemDetermining glucose metabolism kineticsuUsing 18F-FDG micro-PET/CT(MyJoVE Corporation., 2017-05-02) Cochran, BJ; Ryder, WJ; Parmar, A; Klaeser, K; Reilhac, A; Angelis, GI; Meikle, SR; Barter, PJ; Rye, KAThis paper describes the use of 18F-FDG and micro-PET/CT imaging to determine in vivo glucose metabolism kinetics in mice (and is transferable to rats). Impaired uptake and metabolism of glucose in multiple organ systems due to insulin resistance is a hallmark of type 2 diabetes. The ability of this technique to extract an image-derived input function from the vena cava using an iterative deconvolution method eliminates the requirement of the collection of arterial blood samples. Fitting of tissue and vena cava time activity curves to a two-tissue, three compartment model permits the estimation of kinetic micro-parameters related to the 18F-FDG uptake from the plasma to the intracellular space, the rate of transport from intracellular space to plasma and the rate of 18F-FDG phosphorylation. This methodology allows for multiple measures of glucose uptake and metabolism kinetics in the context of longitudinal studies and also provides insights into the efficacy of therapeutic interventions. © 2022 MyJoVE Corporation
- ItemFluorine-18 radiolabelling and in vitro / in vivo metabolism of [18F]D4-PBR111(John Wiley & Sons, Inc, 2019-05-26) Wyatt, NA; Safavi-Naeini, M; Wotherspoon, ATL; Arthur, A; Nguyen, AP; Parmar, A; Hamze, H; Day, CM; Zahra, D; Matesic, L; Davis, E; Rahardjo, GL; Yepuri, NR; Shepherd, R; Murphy, RB; Pham, TQ; Nguyen, VH; Callaghan, PD; Holden, PJ; Grégoire, MC; Darwish, TA; Fraser, BHObjectives The purinergic receptor P2X ligand-gated ion channel type 7 (P2X7R) is an adenosine triphosphate (ATP)-gated ion-channel, and P2X7R is a key player in inflammation. P2X7R is an emerging therapeutic target in central nervous system (CNS) diseases including Alzheimer's disease (AD) and Parkinson's disease (PD), because P2X7R also plays a pivotal role in neuroinflammation. P2X7R represents a potential molecular imaging target for neuroinflammation via biomedical imaging technique positron emission tomography (PET), and several radioligands targeting P2X7R have been developed and evaluated in animals. In our previous work, we have developed and characterized [11C]GSK1482160 as a P2X7R radioligand for neuroinflammation,2 clinical evaluation of [11C]GSK1482160 in healthy controls and patients is currently underway, and the estimation of radiation dosimetry for [11C]GSK1482160 in normal human subjects has been reported.3 Since the half-life (t1/2) of radionuclide carbon-11 is only 20.4 min, it is attractive for us to develop derivatives of [11C]GSK1482160, which can be labeled with the radionuclide fluorine-18 (t1/2, 109.7 min), and a fluorine-18 ligand would be ideal for widespread use.4 To this end, a series of [18F]fluoroalkyl including [18F]fluoromethyl (FM), [18F]fluoroethyl (FE), and [18F]fluoropropyl (FP) derivatives of GSK1482160 have been prepared and examined as new potential P2X7R radioligands. © 2019 The Authors
- ItemImaging capabilities of the Inveon SPECT system using single-and multipinhole collimators(Society of Nuclear Medicine and Molecular Imaging, 2013-09-05) Boisson, F; Zahra, D; Parmar, A; Grégoire, MC; Meikle, SR; Hamze, H; Reilhac, AThe Inveon small-animal SPECT system comes with several types of multipinhole collimator plates. We evaluate here the performance measurements of the Inveon SPECT system using 6 different collimators: 3 dedicated for mouse imaging and 3 for rat imaging. Methods: The measured performance parameters include the sensitivity, the spatial resolution using line sources, the ultra-micro Derenzo phantom, the recovery coefficient and the noise measurements using the National Electrical Manufacturers Association NU-4 image quality phantom, obtained with the 2 reconstruction algorithms available with the Inveon Acquisition Workplace, version 1.5—the 3-dimensional ordered-subset expectation maximization (3DOSEM) and the 3-dimensional maximum a posteriori (3DMAP). Further, the overall performance of the system is illustrated by an animal experiment. Results: The results show that the Inveon SPECT scanner offers a spatial resolution, measured at the center of the field of view, ranging from 0.6 to 1 mm with the collimator plates dedicated to mouse imaging and from 1.2 to less than 2 mm with rat collimator plates. The system sensitivity varies from 29 to 404 cps/MBq for mouse collimators and from 53 to 175 cps/MBq for rat collimators. The image quality study showed that 3DMAP allows better noise reduction while preserving the recovery coefficient, compared with other regularization strategies such as the premature termination of the 3DOSEM reconstruction or 3DOSEM followed by gaussian filtering. Conclusion: The acquisition parameters, such as the collimator set and the radius of rotation, offer a wide range of possibilities to apply to a large number of biologic studies. However, special care must be taken because this increase in sensitivity can be offset by image degradation, such as image artifacts caused by projection overlap and statistical noise due to a higher number of iterations required for convergence. 3DMAP allowed better noise reduction while maintaining relatively constant recovery coefficients, as compared with other reconstruction strategies. © 2013 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
- ItemIn vivo PET imaging with [18F]FDG to explain improved glucose uptake in an apolipoprotein A-I treated mouse model of diabetes(Springer Nature, 2016-05-18) Cochran, BJ; Ryder, WJ; Parmar, A; Tang, S; Reilhac, A; Arthur, A; Charil, A; Hamze, H; Barter, PJ; Kritharides, L; Meikle, SR; Grégoire, MC; Rye, KAType 2 diabetes is characterised by decreased HDL levels, as well as the level of apolipoprotein A-I (apoA-I), the main apolipoprotein of HDLs. Pharmacological elevation of HDL and apoA-I levels is associated with improved glycaemic control in patients with type 2 diabetes. This is partly due to improved glucose uptake in skeletal muscle.© 2016 Springer Nature
- ItemPositron emission tomography and functional characterization of a complete PBR/TSPO knockout(Springer Nature, 2014-11-19) Banati, RB; Middleton, RJ; Chan, RHY; Hatty, CR; Wai-Ying Kam, W; Quin, C; Graeber, MB; Parmar, A; Zahra, D; Callaghan, PD; Fok, S; Howell, NR; Grégoire, MC; Szabo, A; Pham, TQ; Davis, E; Liu, GJThe evolutionarily conserved peripheral benzodiazepine receptor (PBR), or 18-kDa translocator protein (TSPO), is thought to be essential for cholesterol transport and steroidogenesis, and thus life. TSPO has been proposed as a biomarker of neuroinflammation and a new drug target in neurological diseases ranging from Alzheimer’s disease to anxiety. Here we show that global C57BL/6-Tspotm1GuWu(GuwiyangWurra)-knockout mice are viable with normal growth, lifespan, cholesterol transport, blood pregnenolone concentration, protoporphyrin IX metabolism, fertility and behaviour. However, while the activation of microglia after neuronal injury appears to be unimpaired, microglia from GuwiyangWurraTSPO knockouts produce significantly less ATP, suggesting reduced metabolic activity. Using the isoquinoline PK11195, the ligand originally used for the pharmacological and structural characterization of the PBR/TSPO, and the imidazopyridines CLINDE and PBR111, we demonstrate the utility of GuwiyangWurraTSPO knockouts to provide robust data on drug specificity and selectivity, both in vitro and in vivo, as well as the mechanism of action of putative TSPO-targeting drugs. Copyright © 2014, Springer Nature
- ItemThe role of earthquakes and climate in the formation of diamictic sediments in a New Zealand mountain lake(Elsevier, 2018-03-03) Woodward, CA; Slee, A; Gadd, PS; Zawadzki, A; Hamze, H; Parmar, A; Zahra, DWe used Itrax XRF, magnetic susceptibility, grain size, and micro-CT scanning to provide a facies classification for a Late Holocene sediment sequence from Lake Chappa'ai in the Southern Alps, New Zealand. The record contained multiple diamictic layers and our objective was to determine the environmental significance of these deposits. Clast fabric analysis indicated that the diamicts comprise dropstones transported to the centre of the lake by ice rafting. Diamicts belonging to Facies 1 represent rock falls onto lake ice triggered by earthquakes that produced MMI (Modified Mercalli Intensity) > 8 shaking in the catchment. MMI >8 earthquakes may need to occur when the lake has ice cover to produce Facies 1 diamicts. MMI >8 earthquakes in the ice free season or MMI 7–8 earthquakes may also result in an increased flux of large (>1 mm) clasts to the centre of the lake, but may not produce a Facies 1 diamict. More work is required to establish the role of climate related processes on the formation of non-Facies 1 diamicts in Lake Chappa'ai. Climate change may directly lead to diamict formation by changing lake ice cover and facilitating transport of large clasts by anchor ice, or increasing the likelihood of rain on snow events in the spring. Changing ice cover conditions will also affect how mountain lakes record past earthquake events. Lakes that are ice free will not produce earthquake diamicts and lakes that have perennial ice cover may produce a single diamict representing multiple earthquakes if the lake becomes ice free. A reduction in the duration of winter ice cover will also decrease the probability of capturing primary rockfall deposits from earthquakes. Additional data, such as a diatom or chironomid record from Lake Chappa'ai may help to resolve the contribution of climate processes to diamict formation. We should consider the Lake Chappa'ai record as an indicator of minimum earthquake activity until we can disentangle the effects of climate change on non-Facies 1 diamict formation. This study highlights the multiple mechanisms that can lead to diamict formation in mountain lake sediments. These processes should always be considered before attributing the presence of diamict deposits to ice-rafted debris in a pro-glacial lake. This is particularly true in seismically active settings where earthquake triggered rockfalls may lead to diamict formation. Crown Copyright ©2017 Published by Elsevier Ltd
- ItemSelective, high-contrast detection of syngeneic glioblastoma in vivo(Springer Nature, 2020-06-19) Banati, RB; Wilcox, P; Xu, R; Yin, G; Si, E; Son, ET; Shimizu, M; Holsinger, RMD; Parmar, A; Zahra, D; Arthur, A; Middleton, RJ; Liu, GJ; Charil, A; Graeber, MBGlioblastoma is a highly malignant, largely therapy-resistant brain tumour. Deep infiltration of brain tissue by neoplastic cells represents the key problem of diffuse glioma. Much current research focuses on the molecular makeup of the visible tumour mass rather than the cellular interactions in the surrounding brain tissue infiltrated by the invasive glioma cells that cause the tumour’s ultimately lethal outcome. Diagnostic neuroimaging that enables the direct in vivo observation of the tumour infiltration zone and the local host tissue responses at a preclinical stage are important for the development of more effective glioma treatments. Here, we report an animal model that allows high-contrast imaging of wild-type glioma cells by positron emission tomography (PET) using [18 F]PBR111, a selective radioligand for the mitochondrial 18 kDa Translocator Protein (TSPO), in the Tspo−/− mouse strain (C57BL/6-Tspotm1GuMu(GuwiyangWurra)). The high selectivity of [18 F]PBR111 for the TSPO combined with the exclusive expression of TSPO in glioma cells infiltrating into null-background host tissue free of any TSPO expression, makes it possible, for the first time, to unequivocally and with uniquely high biological contrast identify peri-tumoral glioma cell invasion at preclinical stages in vivo. Comparison of the in vivo imaging signal from wild-type glioma cells in a null background with the signal in a wild-type host tissue, where the tumour induces the expected TSPO expression in the host’s glial cells, illustrates the substantial extent of the peritumoral host response to the growing tumour. The syngeneic tumour (TSPO+/+) in null background (TSPO−/−) model is thus well suited to study the interaction of the tumour front with the peri-tumoral tissue, and the experimental evaluation of new therapeutic approaches targeting the invasive behaviour of glioblastoma. © 2020, The Author(s).
- ItemSimultaneous scanning of two mice in a small-animal PET scanner: a simulation-based assessment of the signal degradation(IOP science publishing, 2016-01-21) Reilhac, A; Boisson, F; Wimberley, CA; Parmar, A; Zahra, D; Hamze, H; Davis, E; Arthur, A; Bouillot, C; Charil, A; Grégoire, MCIn PET imaging, research groups have recently proposed different experimental set ups allowing multiple animals to be simultaneously imaged in a scanner in order to reduce the costs and increase the throughput. In those studies, the technical feasibility was demonstrated and the signal degradation caused by additional mice in the FOV characterized, however, the impact of the signal degradation on the outcome of a PET study has not yet been studied. Here we thoroughly investigated, using Monte Carlo simulated [18F]FDG and [11C]Raclopride PET studies, different experimental designs for whole-body and brain acquisitions of two mice and assessed the actual impact on the detection of biological variations as compared to a single-mouse setting. First, we extended the validation of the PET-SORTEO Monte Carlo simulation platform for the simultaneous simulation of two animals. Then, we designed [18F]FDG and [11C]Raclopride input mouse models for the simulation of realistic whole-body and brain PET studies. Simulated studies allowed us to accurately estimate the differences in detection between single- and dual-mode acquisition settings that are purely the result of having two animals in the FOV. Validation results showed that PET-SORTEO accurately reproduced the spatial resolution and noise degradations that were observed with actual dual phantom experiments. The simulated [18F]FDG whole-body study showed that the resolution loss due to the off-center positioning of the mice was the biggest contributing factor in signal degradation at the pixel level and a minimal inter-animal distance as well as the use of reconstruction methods with resolution modeling should be preferred. Dual mode acquisition did not have a major impact on ROI-based analysis except in situations where uptake values in organs from the same subject were compared. The simulated [11C]Raclopride study however showed that dual-mice imaging strongly reduced the sensitivity to variations when mice were positioned side-by-side while no sensitivity reduction was observed when they were facing each other. This is the first study showing the impact of different experimental designs for whole-body and brain acquisitions of two mice on the quality of the results using Monte Carlo simulated [18F]FDG and [11C]Raclopride PET studies. © 2016 Institute of Physics and Engineering in Medicine